Potentiation of BCNU-induced cytotoxicity and sister chromatid exchanges by dibromodulcitol in vitro.
Dibromodulcitol (DBD) is an anticancer agent that is cytotoxic against animal and human brain tumors in vivo. Clinical trials of combination therapy with radiation, DBD, and a nitrosourea have shown some efficacy, but the mechanisms that lead to enhanced cytotoxicity are poorly understood. We investigated the effects of pretreatment with DBD on cell survival and sister chromatid exchange (SCE) caused by subsequent treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells. Pretreatment of 9L cells for 24 hr with 5 microM DBD potentiated the cell kill produced by a 1-hr treatment with BCNU; the dose enhancement ratio was 1.7 at the 10% survival level. Treatment of 9L cells for 24 hr with 1 microM DBD induced 39 +/- 12 SCEs/metaphase. There was a 50-75% increase in BCNU-induced SCEs, compared with BCNU alone, after a 24 hr pretreatment with DBD. Thus DBD potentiation of BCNU cytotoxicity appears to be related to increased DNA damage.
Pulst
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Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Deen
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D000818:Animals; D001932:Brain Neoplasms; D002330:Carmustine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007700:Kinetics; D008936:Mitolactol / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D008936:Mitolactol; D002330:Carmustine